Acute inhibition of Rho-kinase attenuates pulmonary hypertension in patients with congenital heart disease.
This study aimed to determine whether the Rho-kinase-mediated pathway is involved in the pathogenesis of left-to-right shunt-induced pulmonary hypertension and whether fasudil exhibits acute beneficial effects on the hemodynamics of these patients. A total of 12 patients with a mean age of 12.3 years were enrolled in a self-controlled prospective study. All the patients had a diagnosis of congenital heart disease with slight to moderate pulmonary hypertension and were scheduled for transcatheter closure. After placement of the catheters, 30 mg/kg fasudil was injected intravenously over 30 min under room air conditions. Hemodynamic parameters including pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), systemic artery pressure (SAP), systemic vascular resistance (SVR), cardiac input, and blood oxygen saturation were measured and calculated at baseline and 30 min after fasudil injection. After fasudil treatment, PASP decreased to a level 33.03 +/- 6.64% less than baseline value (p < 0.01), and maximal PVR decreased to a level 33.03 +/- 6.64% less than baseline value (p < 0.01). Cardiac input increased to a level 7.7 +/- 5.2% more than baseline value (p < 0.05), and mixed venous oxygen saturation significantly increased to a level 7.7 +/- 5.2% more than baseline value (p < 0.01). The left-to-right shunt ratio (Q(P)/Q(S)) also tended to increase (16.2 +/- 12.5% of baseline value; p < 0.01). Whereas SAP showed only a slight decrease (-1.6 +/- 3.1% of baseline value; p = 0.08), SVR significantly decreased (-10.2 +/- 12.2% of baseline value; p < 0.01), and the PVR/SVR ratio tended to decrease (-23.9 +/- 15.1% of baseline value). In conclusion, Rho-kinase is involved in the pathogenesis of left-to-right shunt-induced pulmonary hypertension, and fasudil is a novel therapeutic approach.
Li
Fuhai
F
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Public Health, Shandong University Qilu Hospital, Jinan, China. fuhai_li@163.com
Xia
Wei
W
Yuan
Shuanghu
S
Sun
Ruopeng
R
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D006330:Heart Defects, Congenital / Q000150:complications*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D007262:Infusions, Intravenous; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000502:physiology; D016896:Treatment Outcome; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; C049347:fasudil